Nearly 46% of women and 33% of men report attempts to lose weight. However, weight cycling - intentional weight loss followed by regain of at least 10Ibs. - occurs in approximately 80% of adults who lose weight;50% of the weight regain occurs within a year. A major focus of the candidate's research is on behavioral and technological strategies to improve long-term weight loss maintenance. With the support of the Midcareer Investigator Award in Patient-Oriented Research (K24), the candidate will expand this focus to an investigation of the biobehavioral processes involved in the failure to maintain a loss and the subsequent weight regain. The proposed study will build on an ongoing randomized clinical trial (SMART study) and collect specimens every 6 months during the 24-month behavioral, weight loss intervention so that the candidate and her multidisciplinary team can prospectively study the subset of individuals who lose and regain at least 10Ibs. during the study. The study's 3 aims are: (1) describe the patterns of weight loss and regain from baseline to 24 months and their effect on insulin resistance (plasma insulin), adipokines (TNFalpha, IL-6, adiponectin, IL-10), and ghrelin and leptin;(2) describe the behaviors related to energy intake and energy expenditure and explore their temporal associations with weight loss and weight gain;and (3) explore whether variation in genes implicated in weight change are related to change in serum level of adipokines and to the behaviors related to weight loss and regain. The mentorship plan will focus on the candidate (PI) and a multidisciplinary cadre of mentees who have been working with her. With the support of the K24 Award, Dr. Burke will work with an interdisciplinary team to advance her knowledge of the inflammatory processes that may occur with weight regain, which may provide the link between obesity, insulin resistance, atherosclerosis and cardiovascular disease;additionally, she will focus on the possible role of genetics in these biobehavioral processes. She will use her ongoing studies to mentor students, fellows and junior faculty on the development of behavioral interventions, the use of technology in interventions and measurement, the conduct of clinical trials, and the role of inflammation and genetics in weight loss and regain. She will develop a mentoring program that follows NINR's strategies for integrating biological and behavioral science for better health, and adopting new technologies for better health care. The proposed study and mentoring strategies will be placed in the context of an area of NINR emphasis - promoting health and preventing disease as it addresses a highly prevalent chronic disorder - overweight and obesity.